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Classic late infantile neuronal ceroid lipofuscinosis (LINCL) is a neurodegenerative disease in which autofluorescent "curvilinear" storage bodies accumulate in tissues from affected patients. Recently, the LINCL gene (CLN2) has been found to code for a pepstatin-insensitive lysosomal protease whose activity is deficient in LINCL specimens. We report the first 2 cases of successful prenatal testing for LINCL by using DNA and enzyme-based methods on amniocytes, and describe a new private mutation in one of the families analyzed. These approaches allow definitive prenatal diagnosis and represent a significant improvement over previous pathological methods.

A family of 5 affected male infants in 2 generations with an X-linked pattern of inheritance is described. All affected infants manifested intractable seizures, severe psychomotor retardation, growth failure, microphallus, and death during infancy. Three of the affected patients had radiological studies that demonstrated findings consistent with pachygyria-agyria and agenesis of the corpus callosum. We believe that this family represents a form of X-linked pachygyria-agyria (lissencephaly) that has not been described previously and suggests a locus for lissencephaly on the X chromosome.

Cyclic AMP (cAMP) metabolism was studied in platelets from a series of 14 patients with fragile X syndrome (fra X) and 21 control individuals. 1-Isobutyl-3-methylxanthine was used to inhibit phosphodiesterase and thus measure cAMP production, prostaglandin E1 was used to assess receptor-mediated cAMP accumulation, and forskolin was used to directly stimulate the catalytic subunit. In patients with fra X, basal production was 63% of that of control subjects (p = 0.019). Prostaglandin E1- and forskolin-stimulated production were 61% (p = 0.039) and 56% (p = 0.012) of that of control subjects, respectively. cAMP production in 8 patients with fra X overlapped the control range, whereas measures of production in 6 patients formed a cluster with values lower than any of the 21 control subjects assayed, suggesting possible biochemical heterogeneity within patients with fra X. Results obtained from the group of patients with fra X suggest possible abnormal function or regulation of the catalytic subunit of adenylate cyclase in at least a subgroup of patients with fra X. Variability of biochemical findings in patients with fra X may reflect the known high variability of the clinical syndrome.